PT86870B - Process for the preparation of a granule and a tablet based on a BETA-LACTAMA ANTIBIOTIC - Google Patents

Abstract

A pharmaceutical tablet is provided containing an amphoteric beta-lactam antibiotic, a cellulose product, being microcrystalline cellulose or microfine cellulose or a mixture of both, and a second disintegrant, being low-substituted hydroxypropylcellulose, which fully disintegrates in water within 60 seconds. When swallowed it shows a bioavailability as good as a pharmacy prepared suspension of the antibiotic. The tablet is compressed from a mixture containing a new granulate which is prepared from the antibiotic substance, microcrystalline cellulose and/or microfine cellulose and water only. Such tablets can also be prepared by using other known tablet disintegrants as the second disintegrant.

Description

The present invention relates to a process ^w *** A for the preparation of a pharmaceutical composition comprising an amphoteric beta-lactam antibiotic. More particularly, the invention relates to a pharmaceutical tablet which disintegrates rapidly when dipped. in water and that, when ingested, results in a high availability of antibiotic *. The invention also relates to a process for preparing this tablet by wet granulation *

Background of the invention «w A

The therapeutic action of a drug on a living organism depends to a considerable extent on its formulation. When administering medications, a lot of pharmaceutical formulation is required ·

The first requirement is a high availability! hence the drug in the composition must be made available to the body in an amount as high as possible and optimal blood levels must be reached in the shortest possible time.

This is a typical requirement in the treatment of infections with an antibiotic composition to which the present invention relates.

AS ** A

A second requirement for pharmaceutical formulations

M ics & to allow administration to the patient without problems. However »the formulation with the highest bioavailability is rarely useful to use and on the other hand» the one that is easy to use is often not satisfactorily available ·

For example! amoxidine θ is the most prescribed beta-lactam antibiotic. A considerable amount of amoxicillin is provided in the form of an aqueous suspension as this form has the best availability. However, these suspensions have several disadvantages!

They must be prepared by the pharmacist shortly before administration to the patient. The suspension must be kept cold in a refrigerator or else it is liable to deteriorate. How much is administered should be measured with a spoon or a cup with the inaccuracy inherent in the dosage volume. Another inconvenience for the patient is the discomfort caused by the viscous sugary liquid and sticky container.

To overcome these disadvantages, other dosage forms, for example capsules or tablets, have become available. However, many patients have serious problems with swallowing this solid dosage form, especially the larger ones. In addition, the bioavailability and the maximum concentration of antibiotics in the blood and the time that this concentration2

traction is achieved are lower than the corresponding aqueous suspensions ·

THE.

When a new pharmaceutical composition is developed} particularly in the form of a tablet} there is still a third category of requirements that must be met: the ingredients must satisfy the requirements of the pharmaceutical preparation process · Amoxicillin, for example ^ presents a standard of very bad fluidity> and this fact combined with its sensitivity to humidity> places serious restrictions on its formulation · It is also important that the tablet has adequate physical and chemical properties in relation to hardness>

»Stability> friability> disintegration time *

In order to satisfy these various requirements, the pharmaceutical industry has at its disposal a wide variety of adjuvants subdivided into diluents) binders and adhesives) disintegrants ₅ lubricants> glidants and fluency promoters as well as dyes ₅ flavors and sweeteners · Ê tareA ** The pharmacist's fa develop pharmaceutical formulations that have certain specific properties ·

A * A Λ

One of the most common pharmaceutical operations is to prepare intimate mixtures of various ingredients. These ingredients must be able to interact with each other during the formulation and therefore cannot be predicted in detail the physico-chemical characteristics of the resulting pharmaceutical composition which can have surprising properties.

State of the art

One way to increase the bioavailability of the antibiotic in tablets is to make it disintegrate more quickly when immersed in water. With the help of disintegrants, dispersible tablets were created that disintegrate in a few minutes or even less when immersed in water.

^- Belgian patent 817515 describes a beta-lactam antibiotic in tablets that disintegrates rapidly in the stomach. The mixture to be compressed contains the beta-lactam antibiotic and urea. Binders or diluents have been omitted that appear to delay disintegration. The resulting tablet is said to disintegrate in a relatively rapid manner, so that the active ingredient is released in about 13 minutes. i

British patent 2084016 describes a tablet containing amoxicillin which is prepared with two disintegrants, microcrystalline cellulose and sodium starch glycolate or cross-linked polyvinylpyrrolidone. However, there is no mention of favorable disintegration behavior or good and unexpected absorption.

Dispersible tablets containing disintegrants form a special category · When placed in a glass of water, they disintegrate quickly forming a fine dispersion that can later be ingested.

Existing dispersible tablets for beta-lactam antibiotics are, however, large in relation to the dose of antibiotic and do not exhibit good disintegration behavior. A well-known amoxicillin tablet containing 5θθ «8 weighs 1260 mg. It disintegrates within 2 minutes and the dispersion contains coarse particles.

Summary of the invention

After extensive experimentation »we developed a tablet suitable for amphoteric beta-lactam antibiotics that uses the combination of disintegrants» microcrystalline cellulose and hydroxypropyl substituted lower cellulose. Microfine cellulose can partially or totally replace microcrystalline cellulose, without affecting the process of the invention or the properties of the products of the invention.

This tablet can easily be swallowed as is or drunk after being dispersed in water. This formulation has an • bioavailability of the antibiotic that is the same as that of the medication—

The corresponding prepared in aqueous suspensions and which is the same for the tablet as swallowed as it is or drunk in the form of a suspension.

These tablets can be prepared by pressing a granulate which is mixed with various adjuvants. The granules contain a beta-lactam antibiotic and microcrystalline and / or microfine cellulose. There is no substantial amount of wet binder in the tablet, at least less than 0.5%, preferably 0-0.1% based on the biotic antibiotic. A part of the microcrystalline and / or microfine cellulose is mixed with the active substance and granulated with water · A or δ part mixed with the granulate together with a second disintegrant, preferably hydroxypropyl substituted lower cellulose or cross-linked polyvinylpyrrolidone and, optionally, other adjuvants . The resulting mixture has good fluidity and can be easily processed in the tablet making press.

Details of the developed dispersible tablet invention contain a beta-lactam amphoteric antibiotic and two different disintegrants, one of which is a cellulose product, for example microcrystalline cellulose or microfine cellulose or a mixture of both and the other is hydroxypropyl substituted lower cellulose. Microcrystalline cellulose δ is the common name for partially depolymerized, purified cellulose occurring in the form of a crystalline powder composed of porous particles. It is a widely used adjuvant, known for example with the AVICEL commercial name.

Lower-substituted hydroxypropylcellulose (1-HPC) is the common name for cellulose which is partially substituted with 2-hydroxypropoxy groups. The degree of substitution for the low-substituted variant, a common pharmaceutical adjuvant, is less than 25% and preferably δ 7-16% · Microfin cellulose (eg Elcema), also known as powdered cellulose, is an alpha-cellulose mechanically processed from materials

- 5 eyes for a tablet containing the present invention:

C T maxmax bioavailability

9,268

9 »258

9,561 of the antibiotic expressed in micro blood after administration. that the value of C, fibrous of plants is reached. It is a common pharmaceutical binder and disintegrant.

In this description and in the appended claims cellulose product ”microcrystalline cellulose and microfine cellulose and mixtures thereof are particularly concerned.

The invention tablet presents a new and valuable combination of very good properties. The most important and surprising property is that the bioavailability of the antibiotic when swallowed is as good as when it is dispersed in water before being taken. The amount of active substance absorbed into the blood is the same in both cases. The bioavailability is the same as that of the known drug prepared in the form of aqueous suspensions. This bioavailability is demonstrated by the hair; following data rec of the 5θθ mg of amoxicillin from the Tablet of the invention swallowed just like the tablet of the invention taken as a dispersion in water a dispersion in water known as a ready-to-take dispersion

C is the maximum concentration max grams per milliliter of

T is the time in minutes in max

Bioavailability is expressed as a number proportional to the area under the graph curve (AUC) that represents the evolution of blood concentration over time.

When immersed in water, the tablet of the invention completely disintegrates within 60 seconds to form an excellent aqueous dispersion. However, its design

- 6 (AUC)

19.0

18.7 tegration takes place slowly enough to make ingesting easily ·

Given that it is known in the literature that a conventional amoxicillin preparation has a great variation in bioavailability between individuals »it is surprising that the tablet of the invention shows only a slight inter-individual variation» regardless of whether the tablet was swallowed as it was or drunk in the form of an aqueous dispersion. This additional advantage may be a consequence of the much improved behavior of the disintegration of the tablet.

The tablets of the invention preferably contain 2-20% by weight of substituted hydroxypropylcellulose »more preferably 7-10% by weight», the percentage being based on the weight of the antibiotic.

An additional aspect of the invention is that only small amounts of disintegrants and other excipients are required which results in a considerably smaller tablet that is easier to swallow when compared to prior art dispersible tablets containing the same amount of antibiotic. . A tablet containing 5θθ mg of amoxicillin has a weight of approximately 937 mg, while tablets of the prior art would weigh 1260 mg.

Thus »according to another characteristic of the invention» the tablet contains a high percentage of active substance »which can be 20-70% by weight» but which is preferably 5θ “ό5% by weight.

The fact that the tablet of the invention can be taken »at the patient's choice» either as a solid tablet or as a liquid suspension »contributes to a better compliance with the prescription by the patient. There is a lower risk of therapy failure due to the patient's reluctance to take the prescribed medication.

There is also an economic advantage to being

A single dosage form is required to produce and store. Suspensions, capsules, sticks, effervescent tablets, etc. have become obsolete for antibiotics that are formulated in accordance with the present invention.

new tablet meets all common pharmaceutical standards regarding hardness, friability and stability. The disintegration time of the larger, higher tablet is slightly longer than the smaller, low dose tablet.

The tablet of the invention is designed for amphoteric beta-lactam antibiotics. Bactam lactam antibiotics comprise penicillins and cephalosporins. The term amphoteric means that the molecule contains the same number of free amino groups and free carboxyl groups. Examples are ampicillin, cephalexin and cefadrine, but amoxicillin is preferably used. Amoxicillin trihydrate is commonly used.

material to be compressed consists of a granulate mixed with various adjuvants. The granulate contains the beta-lactam antibiotic and microscrystalline and / or microfine cellulose. A suitable amount of microcrystalline and / or microfin cellulose in the O granulate is 20-50% by weight, preferably 35-5% by weight based on the weight of the antibiotic. The microcrystalline and / or microfine cellulose, lower-substituted hydroxypropylcellulose and optionally other adjuvants are then mixed with the granulate. An additional suitable amount of microcrystalline cellulose is 4-20% by weight, preferably 8-15% by weight based on the weight of the antibiotic. A suitable amount of low substituted hydroxypropyl cellulose is 2-20% by weight, preferably 7-10% by weight based on the weight of the antibiotic.

A further aspect of the invention relates to a process for the preparation of tablets containing the beta-lactam amphoteric antibiotic in combination with two different disintegrants »one of which is a cellulose product eg microcrystalline cellulose or microfine cellulose or a mixture both. The process comprises preparing a grain »mixing the granulate with other ingredients» and priming the resulting mixture to obtain tablets.

Necessary granulate is obtained using the process comprising the following phases!

The beta-lactam antibiotic is mixed with a part of the microcrystalline cellulose and / or disintegrating microfine as the only adjuvant and granulated with water. It is important that the rest of the disintegrant is retained to be added or granulated when obtained. The resulting wet mass is then treated in the usual manner. The granules obtained are ground, dried, ground again and sieved. The wet granules are well dried in a fluid bed dryer at a temperature below C and preferably below 45 ° C.

The particle size distribution of the granulate appears to contribute to the disintegration behavior of the tablets. A suitable distribution is 100% / 0.7 mm, with not more than 30% (preferably 10%) ≤ 0.5 mm and not more than 50% (preferably 20-40%) <0.15 mm.

A good granulate is obtained, which is easily processed, and has an excellent disintegration pattern. This is surprising, given that microcrystalline cellulose, when used in wet granulation, according to the prior art, is always combined with another adjuvant, particularly the lactose binder. In addition, for beta-lactam antibiotics, especially amoxicillin, wet granulation of the prior art is avoided because these antibiotics are generally sensitive to moisture.

The resulting granulate is then mixed with the remaining part of microcrystalline and / or microfine cellulose, with the second disintegrant and optionally, other adjuvants and is pressed into tablets. Usually the others

- 9 adjuvants are lubricants such as magnesium stearate, fluid promoters such as colloidal silica and flavors and sweeteners.

The quality of the granulate is superior when using 20-50% by weight of microcrystalline and / or microfine cellulose, preferably 35-5% by weight, mixed with 4θ-8θ% water, preferably 50-70% by weight , with all percentages in relation to the weight of the antibiotic.

Another advantage of the invention is that it avoids an organic solvent, with all safety aspects, such as granulation liquid.

The proportion of the granulate used in the mixture to be compressed is such that the total mixture contains 20-70% by weight, preferably 50-65% by weight of the antibiotic.

The amount of microscrystalline cellulose and / or microfine added to the granulate is 4-20% by weight, preferably 8-15% by weight, based on the weight of the antibiotic.

The use of the second disintegrant in the mixture to be pressed is essential for the proper disintegration of the tablet. The optimal disintegrating behavior is achieved when 2-20 wt%, preferably 7-10 wt% of the second disintegrant is used based on the weight of the antibiotic. Examples of compounds that can be used as the second disintegrant are cross-linked polyvinylpyrrolidone (eg Kollidon CL), cross-linked sodium carboxymethylcellulose (eg Ac-Di-Sol), starch or starch derivatives such as sodium starch glycolate (for example Explotab), or combinations with starch (for example Primojel), expandable ion exchange resins, such as Amberlite IRP 88, formaldehyde-casein (for example Esma Spreng), alginates, but preferably the second disintegrant is lower hydroxypropylcellulose substituted or cross-linked polyvinylpyrrolidone. The first substance also increases the strength of the pill

An additional feature of the invention is to avoid wet binders in the tablet. These substances used for their binding properties in wet granulation in quantities of about 1—10% based on the weight of the active substance »comprise acacia gum» gelatin »polyvinyl pyrrolidone, starch (paste and pre-gelatinized), s6 alginate sodium and alginate derivatives »sorbitol» glucose and other resistant sugar and soluble celluloses such as methyl cellulose »hydroxypropylmethylcellulose and hydroxypropylcellulose. If present »their amount is less than 0» 5% by weight »preferably 0—0» 1% based on the weight of the antibiotic.

The process is suitable for all amphoteric beta-lactam antibiotics but is more advantageously applied to amoxicillin.

The invention is further illustrated by the following examples, which are not to be construed as limiting the invention.

The disintegration times given according to Example 39.

referred were me

Example 1

Granules containing amoxicillin

Amoxicillin trihydrate

Microcrystalline cellulose

Water

720 g

288 g

420 ml

The solid components were mixed well and granulated with water · The wet mass was kneaded well for minutes', then ground and air dried at 70 ° C in a fluid bed dryer until the granulate did not contain more than 10 »5% water. The granules were passed through

dried through a 0.8 mm sieve and collected after

The # ta operation.

Example 2

Granules containing amoxicillin

Amoxicillin trihydrate

750 g

Microcrystalline cellulose

150 g

Water

345 ml

A granulate was obtained from these components by the procedure of Example 1.

Example 3

Amoxicillin-containing tablets

Granulate from Example 1

500 g

Microcrystalline cellulose

G

20 G lower-substituted hydroxypropylcellulose

Saccharin

3> 5 g

Aroma s

4.0 g

Colloidal silica

1.5 g

Magnesium stearate

7 »5 g

The granulate was mixed for 10 minutes with other excipients, after which the obtained mixture was pressed to obtain tablets in a rotary press.

dose of Weight diameter toughness time in amoxicillin disintegration 125 mg 234 mg 9 mm 137 N 30 Mon 250 mg 469 mg 11 mm 98 N 50 Mon 5OO mg 937 mg 15 mm 137 N 35 Mon 1000 mg 1874 mg 20 mm 137 N 45 Mon

Aromas 11 g

Colloidal silica

Magnesium stearate

1 »5 g

7.5 g

Tablets were obtained from these components following the procedure of Example 3. Tablets with various dosages of amoxicillin can be prepared. disintegrates in 6θ seconds in water ·

Examples 5—10

Amoxicillin-containing tablets

Granules of Example 1 100 g Microcrystalline cellulose 6.18 g Disintegrant (see following table) 6.18 g Colloidal silica 0.19 g Magnesium stearate 0.93 g

Tablets containing about 592 mg of amoxicillin trihydrate were obtained from these components following the procedure of Example 3

Depending on the specific disintegrant, the resulting primers had the following characteristics:

Example Disintegrating Weight Toughness Disintegration time 5 Amberlite IRP 88 939 mg 105 N 60 sec 6 Potato starch 964 mg 113 N 57 sec 7 Kollidon 955 mg 107 N 26 sec 8 Esma Spreng 925 mg 123 N 56 sec 9 Fxplotab 939 mg 119 N 51 sec 10 L-HPC 925 mg 103 N 33 sec

Friability: 0.2-0.4% Example 11 Granules containing monohydrate cephalexin Cephalexin monohydrate 720 g Microcrystalline cellulose 288 g Water 420 ml

A granulate was obtained from these components following the procedure of Example 1

Examples 12-19

Tablets containing cephalexin monohydrate

Granulate from Example 11 50 3.09 g g Microcrystalline cellulose Disintegrating (see Table below) 3.09 g Colloidal silica 0.10 g Flavors Damascus 0.56 g Vanilla 0.06 g Saccharin 0.56 g Magnesium stearate 0.470 ¹ g

Tablets containing approximately

500 mg of cephalexin monohydrate from these components following the procedure of Example 3 »Depending on the design

specific tegrante the resulting tablets had the following characteristics!

Disintegrating Example Weight Hardness Disintegration time

12 Amberlite IRP 88 817 mg 100 N 30 sec 13 Potato starch 819 mg 120 N 30 sec 14 Ac-Di-Sol 811 mg 110 N 40 sec 15 Kollidon CL 812 mg 120 N 30 sec 16 Esma Spreng 813 mg 90 N 55 sec 17 Explotab 810 mg 130 N 35 sec 18 Primojel 813 mg I30 N 40 sec 19 L-HPC 811 mg 120 N 30 sec

Friabilityí less than 1%

Example 20

Granules containing ampicillin anhydrate

Ampicillin anhydrate 720g

Microcrystalline cellulose 288g

Water 420ml

A granulate was obtained from these components following the procedure of Example 1.

Example 21-25

Pills containing ampicillin anhydrate

Granulate of Example 20 Disintegrating microcrystalline cellulose (see Table a Colloidal silica

Flavors

Damascus

Vanilla

50 3 »θ9 g g follow) 3 »O9 g 0.10 g 0.56 g 0.06 g

«

Magnesium stearate

0.470 g

Tablets containing about 48O mg of ampicillin anhydrate were obtained from these components following the procedure of Example 3 · Depending on the specific disintegrant the resulting tablets had the following characteristics:

Example Disintegrating Weight Toughness Disintegration time 21 Ac-Di-Sol 782 mg 90 N 43 sec 22 Kollidon CL 777 mg 90 N 30 sec 23 Explotab 786 mg 89N 45 sec 24 Primojel 785 mg 101 N 44 sec 25 L-HPC 766 mg 100 N 44 sec

Friability: 0.1-0.2%

Example 26

Granules containing ampicillin trihydrate

Ampicillin trihydrate Microcrystalline cellulose Water

720

288

470 g

ml

A granulate was obtained from sources following the procedure of Example 1.

of these make up

Examples 27-34

Pills containing ampicillin trihydrate

Granulate from Example 26

Disintegrating microcrystalline cellulose (see Table below) Colloidal silica

3.09

3.09

0.10

Flavors

Damascus 0.56 g Vanilla 0.06 g Saccharin 0.56 g Stearate magnesium 0.470 g

Tablets containing about 555 mg of ampicillin trihydrate were obtained from these components following the procedure of Example 3. Depending on the specific disintegrant, the resulting tablets had the following characteristics:

Disintegrating Example Weight Hardness Disintegration time

27 Amberlite IRP 88 910 mg 88 N 53 sec 28 Potato starch 931 mg 115 N 41 sec 29 Ac — Di-Sol 9O6 mg 102 N 46 sec 30 Koilidem CL 902 mg 91 N 21 sec 31 Esma Spreng 893 mg 90 N 42 sec 32 Explotab 89O mg 99 N 33 sec 33 Cousin j e1 913 mg 103 N 28 sec 34 L-HPC 897 mg 103 N 24 sec

Friability: 0.1-0.2%

Example 35

Granules containing cefradin

Cefradin 720 g Microcrystalline cellulose 288 g Water 635 ml

A granulate was obtained from these components following the procedure of Example 1.

- 17 Examples 36-38

Tablets containing cefradin

Granulate from Example 35

Disintegrating microcrystalline cellulose (see table below) Colloidal silica

Flavors

Damascus

Vanilla

Saccharin

Magnesium stearate

Fr

50g

3 · »θ9g

3 »° 9g

0.10g

0.56g

0.06g

0.56g

0.470g

Tablets containing about 500 mg of cefradin were obtained from these components following the procedure of Example 3 · Depending on the specific disintegrant the resulting tablets had the following characteristics:

Example Disintegrating Weight Toughness Disintegration time 36 Kollidon CL 888 mg 108 N 32 sec 37 Explotab 881 mg 107 N 60 sec 38 L — HPC 879 mg 111 N 62 sec

Friability! 0.5%

Example 39

Measurement of tablet disintegration time

The test tablet is immersed in 50 ml of water at 20 ° C. After 30 s the vessel is oscillated so that the liquid starts to swirl and no disintegration residues are visible. Once all the large residues have disappeared, time is recorded and the suspension is passed through a 0.71 mm sieve. The values shown are

the average of at least two measurements ·

Example 40

200 g of amoxicillin trihydrate were mixed with 80 g of microfine cellulose (EECEMA G400) and 150 ml of water * The resulting wet mass was kneaded for 20 minutes, sieved through a 2 mm mesh sieve and dried z- O in a fluid bed dryer at about 60 C for about an hour until the granulate does not contain more than 10.5% by weight of water »The dry granulate obtained was sieved through a 0.8 mm mesh sieve and collected.

Example 41

:O s in granulate of Example 40 3> O9 g in microfine cellulose (ELCEMA G400) 3 »O9 g in 1-HPC 0.1 g in colloidal silica 0.56 g in saccharin 0.62 g in scents 0.47 g in magnesium stearate

granulate was mixed for 10 minutes with the other excipients, after which the mixture obtained was compressed into tablets in a rotary press · The 960 mg tablets obtained had a hardness of 106 N and disintegrated in water in a period of 40 seconds.

Claims (5)

Process for the preparation of a granulate containing an amphoteric antibiotics of beta-lactam caracterí Zado by (a) mixing the antibiotic with microcrystalline or microfine cellulose or a mixture of both and water _s and granulating the resultant wet mass for obtain a granulate and (b) grind »dry» grind and sieve the granulate. _ Process according to claim 1, characterized in that the granular mixture contains 20-50%, preferably 35-45% by weight of the cellulose product based on the weight of the antibiotic. - 3 ^a - Process according to either of Claims 1 and 2, characterized in that the granular mixture contains from 0% by weight to 0> 5% by weight, preferably 0% by weight to 0 »1% by weight, of a wet binder substance» with based on the weight of the antibiotic. - 4 * - Process for the preparation of a tablet containing an amphoteric beta-lactam antibiotic characterized by: (a) mixing the granulate prepared according to any of claims 1 to 3 with the microcrystalline or microfine cellulose disintegrant or a mixture of both, a second disintegrant and optionally other excipients (b) compressing the mixture. Process according to claim 4, characterized in that the mixture to be compressed contains 20—70%> preferably by weight of the antibiotic based on the weight of the mixture. - 6® **. Process according to claim 4 or 5, characterized in that the second disintegrant is a lower-substituted hydroxypropyl cellulose. - 7th _ I Process according to claims 4 or 5 »characterized in that the second disintegrant is cross-linked polyvinylpyrrolidone. - 8th 21 Process according to any of claims 4 to 7, characterized in that the granulate is mixed with 4-20% by weight, preferably 8-15% by weight of the cellulose product based on the weight of the antibiotic » 9. A process according to any one of claims 4 to 8, characterized in that the granulate is mixed with 2-20% by weight, preferably 7-10% by weight of substituted hydroxypropylcellulose or polyvinylpyrrolidone cross-linked based on the weight of the antibiotic. - 10® * ». Process according to claim 4, characterized in that 24-70% by weight, preferably 43-60% by weight of the cellulose product and 2-20% by weight, preferably 7-10% by weight of lower hydroxypropylcellulose, are incorporated - -substituted, with all percentages based on the weight of the antibiotic. 11. A process according to claim 5, characterized in that 24-70% by weight, preferably 43-60% by weight of the cellulose product and 2-20% by weight, preferably 7-10% by weight, are incorporated. of ingested-substituted hydroxypropylcellulose, with all percentages based on the weight of the antibiotic.